Abstract
Large structurally diverse peptidomimetic chemical libraries have been very useful tools in chemical biology and drug discovery for the identification of therapeutically important compounds with higher affinity and improved pharmacological properties against different protein targets.
Here we describe a simple and general method for the submonomer solid phase synthesis of large one bead-one compound (OBOC) peptidomimetic libraries of structurally diverse compounds that can be encoded by mass or genetic methods.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85(14):2149–2154
Vaino A, Janda K (2000) Solid-phase organic synthesis: a critical understanding of the resin. J Comb Chem 2(6):579–596
Tempest PA, Brown SD, Armstrong RW (1996) Solid-phase, parallel syntheses by Ugi multicomponent condensation. Angew Chem Int Ed Engl 35:640–642. https://doi.org/10.1002/anie.199606401
O’Connell KMG, Galloway WRJD, Ibbeson BM, Isidro-Llobet A, O’Connor CJ, Spring DR (2011) In: Toy PH, Lam Y (eds) Diversity-oriented synthesis, in solid-phase organic synthesis: concepts, strategies, and applications. Wiley, Hoboken. https://doi.org/10.1002/9781118141649.ch4
Schreiber SL (2000) Target-oriented and diversity-oriented organic synthesis in drug discovery. Science 287:1964–1969
Tan DS (2005) Diversity-oriented synthesis: exploring the intersections between chemistry and biology. Nature Chem Biol 1:74–84
Lam KS, Lebl M, Krchnak V (1997) The “one-bead-one-compound” combinatorial library method. Chem Rev 97:411–448
Lam KS, Salmon SE, Hersh EM, Hruby VJ, Kazmierski WM, Knapp RM (1991) A new type of synthetic peptide library for identifying ligand-binding activity. Nature 354:82–84
Kodadek T (2010) Rethinking screening. Nat Chem Bio 6:162–165
Figliozzi GM, Goldsmith R, Ng SC, Banville SC, Zuckermann RN (1996) Synthesis of N-substituted glycine peptoid libraries. Methods Enzymol 267:437–447
Uno T, Beausoleil E, Glodsmith RA, Levine BH, Zuckermann RN (1999) New submonomers for poly N-substituted glycines (peptoids). Tet Lett 40:1475–1478
Zuckermann RN, Kerr JM, Kent SBH, Moos WH (1992) Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis. J Am Chem Soc 114:10646–10647
Zuckermann RN, Kodadek T (2009) Peptoids as potential therapeutics. Curr Opin Mol Ther 11:299–307
Clark MA, Acharya RA et al (2009) Design, synthesis and selection of DNA-encoded small-molecule libraries. Nat Chem Biol 5:647–654
MacConnell AB, McEnaney PJ, Cavett VJ, Paegel BM (2015) DNA-encoded solid-phase synthesis: encoding language design and complex oligomer library synthesis. ACS Combinatorial Science 17(9):518–534
Gao Y, Kodadek T (2013) Synthesis and screening of stereochemically diverse combinatorial libraries of peptide tertiary amides. Chem Biol 20:360–369
Aditya A, Kodadek T (2012) Incorporation of heterocycles into the backbone of peptoids to generate diverse peptoid-inspired one bead one compound libraries. ACS Comb Sci 14(3):164–169
Rizzo S, Wakchaure V, Waldmann H (2014) Natural product-derived and natural product-inspired compound collections. In: Hanessian S (ed) Natural products in medicinal chemistry. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. https://doi.org/10.1002/9783527676545.ch02
Pye CR, Bertin MJ, Lokey RS, Gerwick WH, Linington RG (2017) Retrospective analysis of natural products provides insights for future discovery trends. PNAS 114:5601–5606
Aquino C, Sarkar M, Chalmers MJ, Mendes K, Kodadek T, Micalizio GC (2012) A biomimetic polyketide-inspired approach to small-molecule ligand discovery. Nat Chem 4(2):99–104
Sarkar M, Liu Y, Morimoto J, Peng H, Aquino C, Rader C, Chiorazzi N, Kodadek T (2014) Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates. Chem Biol 21(12):1670–1679
Kaiser E, Colescott RL, Bossinger CD, Cook PI (1970) Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem 34:595–598
Wrenn SJ, Weisinger RM, Halpin DR, Harbury PB (2007) Synthetic ligands discovered by in vitro selection. J Am Chem Soc 129:13137–13143
Vojkovsky T (1995) Detection of secondary amines on solid phase. Pept Res 8:236–237
Sarkar M, Pascal BD, Steckler C, Aquino C, Micalizio GC, Kodadek T, Chalmers MJ (2013) Decoding split and pool combinatorial libraries with electron-transfer dissociation tandem mass spectrometry. J Am Soc Mass Spectrom 24(7):1026–1036
Udugamasooriya DG, Dineen SP, Brekken RA, Kodadek T (2008) A peptoid “antibody surrogate” that antagonizes VEGF receptor 2 activity. J Am Chem Soc 130(17):5744–5752
Simpson LS, Kodadek T (2012) A cleavable scaffold strategy for the synthesis of one-bead one-compound cyclic peptoid libraries that can be sequenced by tandem mass spectrometry. Tetrahedron Lett 53:2341–2344
Acknowledgment
The authors would like to thank Professor Glenn C. Micalizio and Professor Thomas Kodadek for their guidance and advice throughout CA’s and MS’s post-graduate studies.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Aquino, C., Sarkar, M. (2022). One Bead-One Compound (OBOC) Peptidomimetic-Encoded Library Synthesis via Split-and-Pool Methods. In: Israel, D., Ding, Y. (eds) DNA-Encoded Chemical Libraries. Methods in Molecular Biology, vol 2541. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2545-3_15
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2545-3_15
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2544-6
Online ISBN: 978-1-0716-2545-3
eBook Packages: Springer Protocols